Keratins mediate localization of hemidesmosomes and repress cell motility.
Keratins mediate localization of hemidesmosomes and repress cell motility.
复制标题
DOI：
10.1038/jid.2012.256
复制
发表时间：
2013-01
影响因子：
6.5
通讯作者：
Magin, Thomas M.
中科院分区：
文献类型：
--
作者：
Seltmann, Kristin;Roth, Wera;Kroeger, Cornelia;Loschke, Fanny;Lederer, Marcell;Huettelmaier, Stefan;Magin, Thomas M.
角蛋白-半桥粒相互作用对于包括表皮在内的几种上皮细胞中的细胞-基质粘附和迁移至关重要。组成蛋白质的突变通过破坏粘附复合物而引起严重的起泡性皮肤疾病。尽管有广泛的研究，角蛋白在半桥粒组装和维持中的作用仅被部分理解。在这里，我们解决这个问题，在角质形成细胞中，所有角蛋白基因组工程耗尽。出乎意料的是，这样的角质形成细胞保持了正常对应物的许多特征。然而，整个角蛋白细胞骨架的缺失导致半桥粒斑块中的网蛋白的丢失和半桥粒跨膜核心沿着基底膜区的分散。为了研究功能后果，我们进行了迁移和粘附测定。这些结果表明，在不存在角蛋白的情况下，角质形成细胞更快地粘附到ECM基底上，并且与野生型细胞相比迁移快约2倍。单一角蛋白对K5和K14的再表达完全逆转了上述表型。我们的数据揭示了一种新的角蛋白在维持半桥粒上游的果胶与表皮稳态和发病机制的影响。他们支持这样的观点，即在上皮-间充质转化期间观察到的角蛋白的下调支持肿瘤细胞的迁移和侵袭行为。
The keratin-hemidesmosome interaction is crucial for cell-matrix adhesion and migration in several epithelia including the epidermis. Mutations in constituent proteins cause severe blistering skin disorders by disrupting the adhesion complex. Despite extensive studies, the role of keratins in hemidesmosome assembly and maintenance is only partially understood. Here, we address this issue in keratinocytes in which all keratins are depleted by genome engineering. Unexpectedly, such keratinocytes maintain many characteristics of normal counterparts. The absence of the entire keratin cytoskeleton, however, leads to loss of plectin from the hemidesmosomal plaque and scattering of the hemidesmosome transmembrane core along the basement membrane zone. To investigate the functional consequences, we performed migration and adhesion assays. These revealed that in the absence of keratins, keratinocytes adhere much faster to ECM substrates and migrate ~2 times faster compared to wildtype cells. Re-expression of the single keratin pair K5 and K14 fully reversed the above phenotype. Our data uncover a novel role of keratins in the maintenance of hemidesmosomes upstream of plectin with implications for epidermal homeostasis and pathogenesis. They support the view that the downregulation of keratins observed during epithelial-mesenchymal transition supports the migratory and invasive behavior of tumor cells.
登录
查看更多内容
影响因子：
3.3
作者：
Koster, J;van Wilpe, S;Sonnenberg, A
通讯作者：
Sonnenberg, A
DOI：
10.1038/jid.2009.439
发表时间：
2010-06
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.3
作者：
Nikolopoulos, SN;Blaikie, P;Giancotti, FG
通讯作者：
Giancotti, FG
影响因子：
7.5
作者：
Gu, Li-Hong;Coulombe, Pierre A.
通讯作者：
Coulombe, Pierre A.
影响因子：
6.5
作者：
Kippenberger, S;Loitsch, S;Bernd, A
通讯作者：
Bernd, A